Effects Of Reeler and Dab1 Mutations On The Lateral Cervical Nucleus

Reelin is a secreted protein essential for the migration and proper positioning of neurons during central nervous system development.  The binding of Reelin to Apolipoprotein E receptor 2 and very low density lipoprotein receptor leads to tyrosine phosporylation of Disabled-1 (Dab1), which propagates the downstream signal within the neurons bearing these receptors.  Previous studies found that  reeler and dab1 mutant mice have aberrantly positioned dorsal horn neurons and altered behavioral changes: thermal hyperaglesia and mechanical insensitivity. Additionally, these mutants have a 40-60% reduction in the lateral spinal nucleus (LSN) neurons.  Based on these observations, their common location in the dorsolateral funiculus, and importance in transmitting nociceptive information, we hypothesized that  neurons of the lateral cervical nucleus (LCN) will sustain similar positioning errors as LSN neurons. We used NeuN immunohistochemical experiments to localize LCN neurons in cervical spinal cord segments 1-2 from wildtype and reelerpairs, and dab1+/+, dab1 ^ß-gal+/-, and dab1 ^ß-gal-/- mice. Additionally, X-gal histochemical reactions localized the presence of the ß-galactosidase within the dab1 ^ß-gal+/- and -/- mice.  Preliminary analyses found dab1 ^ß-gal-/- mice contain, on average, 40% fewer neurons in the LCN than the controls. These results suggest that the Reelin signaling pathway affects the positioning of LCN neurons. and likely contributes to the alterations in nociceptive processing.